Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

Analysis of the metabolic profile and comorbidities in women with endometriosis before and after surgical treatment / Análise do perfil metabólico e comorbidades em mulheres com endometriose antes e depois do tratamento cirúrgico

Aim: this study aimed to evaluate the effects of surgical treatment for endometriosis on the metabolic profile of women diagnosed with deep endometriosis. Methods: we conducted a prospective observational study with a sample of 30 women in the menacme diagnosed with deep endometriosis who underwent videolaparoscopic surgery in a reference center in Brazil between October 2020 and December 2021. A total of 30 women performed clinical and laboratory tests regarding their metabolic profile on two occasions, during preoperative tests and six months after video-laparoscopy. Results: patients had lower average levels of Total Cholesterol (TC), Low-Density Cholesterol (LDL-c), Triglycerides (TGC), and Fasting Glycemia (FG) after the surgical procedure. The average TC level was 8.2% lower after surgery, LDL-c was 12.8% lower, TGC was 10.9% lower, and FG was 7.3% lower. The results showed a statistically significant difference for all these parameters (p < 0.001). Conclusions: video-laparoscopy was associated with a favorable lipid profile compared to the preoperative lipid profile, with a significant improvement in the average levels of LDL-c, HDL-c, TC, TGC, and FG. Long-term follow-up studies are needed to determine whether surgical treatment for endometriosis can improve the metabolic parameters of women with endometriosis and favor a lower predisposition to atherogenesis.

Objetivo: Aeste estudo teve como objetivo avaliar os efeitos do tratamento cirúrgico da endometriose no perfil metabólico de mulheres com diagnóstico de endometriose profunda. Métodos: foi realizado um estudo observacional prospectivo com uma amostra de 30 mulheres na menacme, com diagnóstico de endometriose profunda, que foram submetidas à videolaparoscopia em um centro de referência no Brasil, entre outubro de 2020 e dezembro de 2021. As mulheres realizaram exames clínicos e laboratoriais quanto ao seu perfil metabólico em duas ocasiões, durante exames pré-operatórios e seis meses após a videolaparoscopia. Resultados: as pacientes apresentaram níveis médios mais baixos de Colesterol Total (CT), Colesterol de Baixa Densidade (LDL-c), Triglicerídeos (TGC) e Glicemia de Jejum (GJ) após o procedimento cirúrgico. O nível médio de CT foi 8,2% menor após a cirurgia, o LDL-c foi 12,8% menor, o TGC foi 10,9% menor e a GJ foi 7,3% menor. Os resultados mostraram diferença estatisticamente significativa para todos esses parâmetros (p < 0,001). Conclusões: a videolaparoscopia foi associada a um perfil lipídico favorável em comparação ao perfil lipídico pré-operatório, com melhora significativa nos níveis médios de LDL-c, HDL-c, CT, TGC e GJ. Estudos de acompanhamento a longo prazo são necessários para determinar se o tratamento cirúrgico da endometriose pode melhorar os parâmetros metabólicos de mulheres com endometriose e favorecer uma menor predisposição à aterogênese.

Ângulo de fase como preditor de massa muscular em pacientes com doença inflamatória intestinal / Phase angle as a predictor of muscle mass in patients with inflammatory bowel disease

ABSTRACT Malnutrition/sarcopenia is frequent in patients with inflammatory bowel diseases (IBD), and results in muscle catabolism, impacting treatment response, postoperative complications, and quality of life. Objective: This study aims to assess whether the phase angle (PhA) is a parameter for predicting reduced muscle mass in patients with IBD. Methods: Adult patients with IBD were included in this cross-sectional study. For the estimation of muscle mass and the calculation of the PhA, we used bioelectrical impedance analysis (BIA). Crohn's disease (CD) and ulcerative colitis (UC) activity scores were defined using the Harvey-Bradshaw index and partial Mayo score, respectively. The area under the ROC curve was calculated to identify the PhA cut-off point for reduced muscle mass. Results: The sample consisted of 145 patients, with 39 (26.9%) with IBD in the active phase. There was a correlation of the PhA with skeletal muscle mass (SMM) (rs 0.35, P<0.001) and with the skeletal muscle mass index (SMI) (rs 0.427, P<0.001), and the associations remained in the most active form (moderate or severe) of IBD. The ROC curve analysis indicated that the cut-offs points of the PhA ≤5.042 for female and PhA ≤6.079 for male can be used to predict muscle mass reduction. Conclusion: The PhA can be considered a predictor of muscle mass reduction in IBD patients, and we can use it for screening and monitoring the evolution of malnutrition.

RESUMO A desnutrição/sarcopenia é frequente em pacientes com doenças inflamatórias intestinais (DII), resultando em catabolismo muscular, com impacto nas respostas aos tratamentos, complicações cirúrgicas e na qualidade de vida. Objetivo: Este estudo tem como objetivo, avaliar se o ângulo de fase (AF) é um parâmetro para a predição de redução de massa muscular em pacientes com DII. Métodos: Pacientes adultos com DII foram incluídos neste estudo transversal. A estimativa da massa muscular e o cálculo do AF foram realizados a partir do exame de bioimpedância elétrica (BIA). As atividades da doença de Crohn e retocolite ulcerativa foram definidas pelo índice Harvey-Bradshaw e escore parcial de Mayo, respectivamente. A área de curva ROC foi calculada para identificar o ponto de corte do AF para a massa muscular reduzida. Resultados: A amostra foi composta por 145 pacientes, sendo 39 (26.9%) com DII em fase ativa. Houve correlação do AF com massa muscular esquelética (MME) (rs 0.35, P<0.001) e com o índice de massa muscular esquelética (IMME) (rs 0.427, P<0.001), mantendo-se as associações na forma mais ativa (moderada ou grave) da DII. A análise da curva ROC indicou que os pontos de corte de AF ≤5.042 para mulheres e ≤6.079 para homens podem ser usados para prever a redução da massa muscular. Conclusão: O AF pode ser considerado um preditor de redução de massa muscular nos pacientes com DII e ser utilizado para triagem e acompanhamento da evolução da desnutrição.

Uma pesquisa de manejo médico e neuropsiquiátrico em uma coorte brasileira de pacientes com doença inflamatória intestinal (DII) / A medical and neuropsychiatric management survey in a brazilian cohort of patients with inflammatory bowel disease (ibd)

ABSTRACT Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions.

RESUMO A doença inflamatória intestinal (DII) pode ser acompanhada por vários distúrbios neurológicos. Desde 2004, iniciamos uma coorte brasileira para avaliar complicações neuropsiquiátricas em pacientes com DII. Mudanças na estratégia terapêutica e diferenças na prevalência e relevância dos transtornos neuropsiquiátricos têm sido relatadas na literatura. Realizamos uma breve pesquisa relatada pelos pacientes sobre o manejo médico da DII (com foco especial no manejo neuropsiquiátrico) e suas complicações. Durante o período de 01/09/2021 a 31/08/2022, 279 pacientes com DII responderam à pesquisa (128 pacientes com retocolite ulcerativa e 151 com doença de Crohn). Esta é a primeira pesquisa de gestão médica que visa verificar o nível de percepção dos pacientes com DII acerca de suas condições neuropsiquiátricas. Encontramos uma alta prevalência de comorbidades neurológicas (59%), psiquiátricas (32%) e neuropsiquiátricas (69%). Há uma discrepância marcante entre os achados de distúrbios neurológicos relatados em nossos estudos durante os primeiros 10 anos da coorte em comparação com a percepção/conhecimento atual entre os pacientes da presente pesquisa de manejo. Os pacientes tendem a ter uma melhor compreensão das condições que afetam o sistema nervoso central do que as que afetam o sistema nervoso periférico.

Taxas de hospitalização, uso de biológicos e cirurgias em doenças inflamatórias intestinais: uma análise comparativa entre os sistemas público e privado de saúde em centro de referência da América Latina / Hospitalization, use of biologics and surgery rates in inflammatory bowel diseases: a single-centre comparative analysis between public and private healthcare systems in a tertiary unit from latin america

ABSTRACT Background: Inflammatory bowel diseases (IBD) have rising incidence and prevalence rates globally. In IBD, there are scarce stu­dies comparing differences between patients according to socioeconomic status. Our aim was to comparatively evaluate hospitalizations, use of biologics and rates of surgery in patients with IBD between public and private healthcare systems. Methods: Single-center retrospective cohort study in patients with IBD from a tertiary referral unit from Latin America, between 2015 and 2021. CD and UC patients were classified into two subgroups: public and private systems. Demographic characteristics, hospitalizations, need for surgery and biologics were compared. Results: A total of 500 patients were included, 322 with CD and 178 with UC. CD-related hospitalizations were frequently observed in both healthcare systems (76.28% in private and 67.46% in public). More than half of the patients had been submitted to one or more CD-related abdominal surgery, with no significant difference between the subgroups. Although there was no difference in the rates of use of biological therapy in CD subgroups, infliximab was more used in the public setting (57.69% vs 43.97%). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%) as well as the rates of colectomy (public: 16.83%, private: 19.48%). Biologics were prescribed almost twice as often in private as compared to public (45.45 vs 22.77%). Conclusion: There were no differences in the rates of hospitalization and abdominal surgery between the systems. In patients with UC, there was greater use of biological therapy in the private healthcare setting.

RESUMO Contexto: As doenças inflamatórias intestinais (DII) têm taxas crescentes de incidência e prevalência em todo o mundo. Na DII, são escassos os estudos comparando as diferenças entre os pacientes de acordo com o nível socioeconômico. Objetivo: Nosso objetivo foi avaliar comparativamente as hospitalizações, o uso de biológicos e as taxas de cirurgia em pacientes com DII entre os sistemas público e privado de saúde. Métodos: Estudo de coorte retrospectivo unicêntrico em pacientes com DII de uma unidade terciária de referência da América Latina, entre 2015 e 2021. Os pacientes com DC (doença de Crohn) e retocolite ulcerativa foram classificados em dois subgrupos: sistema público e privado. Características demográficas, hospitalizações, necessidade de cirurgia e biológicos foram comparadas. Resultados: Foram inclusos 500 pacientes, sendo 322 com DC e 178 com retocolite ulcerativa. Internações por DC foram frequentes em ambos os sistemas de saúde (76,28% na rede privada e 67,46% na rede pública). Mais da metade dos pacientes havia sido submetida a uma ou mais cirurgias abdominais relacionadas à DC, sem diferença significativa entre os subgrupos. Embora não tenha havido diferença nas taxas de uso de terapia biológica nos subgrupos de DC, o infliximabe foi mais utilizado no ambiente público (57,69% vs 43,97%). Não houve diferença nas internações relacionadas a retocolite ulcerativa entre os subgrupos (público 30,69% e privado 37,66%) e nas taxas de colectomia (público: 16,83%, privado: 19,48%). Os biológicos foram prescritos quase duas vezes mais no privado do que no público (45,45 vs 22,77%). Conclusão: Não houve diferença nas taxas de internação hospitalar e de cirurgia abdominal entre os sistemas. Nos pacientes com retocolite ulcerativa, houve maior utilização da terapia biológica no setor privado de saúde.

Composição da gordura corporal em pacientes com doenças inflamatórias intestinais: um estudo comparativo entre dobras cutâneas e ultrassonografia / Body fat composition in patients with inflammatory bowel diseases: a comparative study between skinfolds and ultrasonography

ABSTRACT Background: Inflammatory bowel diseases (IBD) are associated with important changes in nutritional status. Objective: The aim of the study was to compare body fat composition between two anthropometric methods: skinfolds and ultrasonography, in patients with IBD. Methods: Single-center cross-sectional study with IBD patients in remission or active disease. For the agreement analysis between the body fat assessment methods, the Bland Altman method was used. Results: A total of 101 patients with IBD were included, 75 with Crohn's disease and 26 with ulcerative colitis. Approximately 56% of the patients with Crohn's disease and 65.4% of those with ulcerative colitis had a body fat composition above normal levels, with no significant difference between the diseases (P=0.63). The Bland-Altman concordance analysis showed that the methods for assessing the percentage of fat by the adipometer and ultrasound were not in full agreement (P=0.001), despite both presented good correlation (CC 0.961; P=0.000). Conclusion: The analysis of body fat percentage in patients with IBD was different between the skinfolds and ultrasound. Both methods can be used to assess the of body fat percentage of patients with IBD. However, monitoring of body fat sequentially and longitudinally should always be performed using the same method throughout the disease course. Prospective longitudinal studies are warranted to precisely define the role of these two methods of measuring body composition in patients with IBD.

RESUMO Contexto: As doenças inflamatórias intestinais (DII) estão associadas a alterações importantes no estado nutricional. Objetivo: O objetivo do estudo foi comparar a composição da gordura corporal entre dois métodos antropométricos: dobras cutâneas e ultrassonografia, em pacientes com DII. Métodos: Estudo transversal de centro único com pacientes com DII em remissão ou doença ativa. Para a análise de concordância entre os métodos de avaliação da gordura corporal foi utilizado o método de Bland-Altman. Resultados: Foram incluídos 101 pacientes com DII, 75 com doença de Crohn e 26 com colite ulcerativa. Aproximadamente 56% dos pacientes com doença de Crohn e 65,4% daqueles com colite ulcerativa apresentaram composição de gordura corporal acima dos níveis normais, sem diferença significativa entre as doenças (P=0,63). A análise de concordância de Bland-Altman mostrou que os métodos de avaliação do percentual de gordura pelo adipômetro e ultrassonografia não foram totalmente concordantes (P=0,001), apesar de ambos apresentarem boa correlação (CC 0,961; P=0,000). Conclusão: A análise do percentual de gordura corporal em pacientes com DII foi diferente entre as dobras cutâneas e a ultrassonografia. Ambos os métodos podem ser usados para avaliar o percentual de gordura corporal de pacientes com DII. Entretanto, o monitoramento da gordura corporal de forma sequencial e longitudinal deve ser sempre realizado utilizando o mesmo método durante todo o curso da doença. Estudos longitudinais prospectivos são necessários para definir com precisão o papel desses dois métodos de medição da composição corporal em pacientes com DII.

Endothelial Microparticles: Markers of Inflammatory Response After Sutureless Valve Implantation

ABSTRACT Introduction: Systemic inflammatory response syndrome (SIRS) is related to increased circulating endothelial microparticles (EMP). Objective: The aim of this study was to compare the plasma concentration of EMP between patients undergoing aortic valve replacement with conventional bioprosthesis implantation and Perceval™ S (LivaNova) and to evaluate its impact on the inflammatory response in the short-term follow-up. Methods: This is a randomized clinical trial with 24 patients submitted to isolated aortic valve replacement divided into two groups: Perceval™ S (Group P) and conventional bioprostheses (Group C). Incidence of severe SIRS (three or more criteria) in the first 48 hours postoperatively, EMP release profile, interleukins (IL) 6 and 8, C-reactive protein, and procalcitonin were analyzed preand postoperatively at 24 hours and three months. Results: There were 24 patients (12 in each group), mean age was 69.92±5.17 years, 83.33% were female, the incidence of severe SIRS was 66.7% and 50% in groups C and P, respectively (P=0.68), and EMP showed a significant increase in the 24-hour postoperative period (P≤0.001) and subsequent decrease in the three-month postoperative period (P≤0.001), returning to baseline levels. For IL-6 and IL-8, there was a greater increase in group C at 24 hours postoperatively (P=.0.02 and P<0.001). Conclusion: The incidence of severe SIRS was similar in both groups, with significantly higher levels of IL-6 and IL-8, at the 24-hour postoperative period, in group C, however with higher levels of EMP in group P, and subsequent return to baseline levels at the three-month postoperative period in both groups.

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats

Purpose: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. Methods: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. Results: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). Conclusions: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Rickettsia rickettsii and Rickettsia typhi in hospitalized children diagnosed with Pediatric Multisystemic Inflammatory Syndrome in Merida, Yucatan

Abstract Multisystem Inflammatory Syndrome in Children (MIS-C) presents with fever, fatigue, elevated inflammatory markers (acute phase reactants), and a history of exposure to SARS-CoV-2 or positive antibodies to SARS-CoV-2. As the COVID-19 pandemic unfolded, the risk of MIS-C in the pediatric population increased. However, exposure to other viruses and the presence of SARS-CoV-2 positive antibodies in children hospitalized for various pathogen-associated illnesses will also remain common and may complicate differential diagnoses with diseases endemic to the region such as rickettsial diseases. The objective was to highlight the desirability of medical personnel systematically incorporating rickettsiosis as a differential diagnosis for MIS-C when studying a child with fever, non-specific symptoms, and elevated inflammatory markers. In conclusion MIS-C should be considered in children with elevated inflammatory markers when there is a history of COVID-19 and they also meet criteria that have already been established by international agencies, such as CDC and WHO

Eficacia y seguridad del supositorio Proctokinasa® en el tratamiento de la enfermedad inflamatoria pélvica aguda

Introducción: La enfermedad inflamatoria pélvica aguda es una entidad frecuente en mujeres jóvenes en edad reproductiva, y constituye la causa principal de infertilidad. La búsqueda de un tratamiento antiinflamatorio eficaz y seguro que alivie el dolor, evite complicaciones y secuelas, es una prioridad para su tratamiento. Objetivo: Evaluar la eficacia y seguridad del tratamiento con Proctokinasa® en la enfermedad inflamatoria pélvica aguda grados I y II. Materiales y métodos: Se desarrolló un ensayo clínico, controlado, abierto, de enero de 2017 a enero de 2018, que incluyó 76 pacientes con diagnóstico de enfermedad inflamatoria pélvica aguda en la atención primaria de salud, quienes fueron asignadas aleatoriamente a dos grupos de tratamiento: grupo principal Proctokinasa®, que recibió una unidad/8 h por 2 días, y el grupo Piroxicam, un supositorio de 20 mg/24 h por 7 días. La antibioticoterapia oral recomendada se inició simultáneamente. Se evaluó la respuesta clínica y ecográfica al tratamiento. Los eventos adversos fueron evaluados. Resultados: Se constató respuesta clínica a partir de las 72 horas de tratamiento en más del 50 % de las pacientes en ambos grupos, y fue del 100 % de los casos para el grupo Proctokinasa® en las dos últimas evaluaciones realizadas (días 10 y 15). Se evidenció la remisión de las alteraciones ecográficas en el 96,9 % del grupo Proctokinasa®. Los eventos adversos fueron escasos y leves. Conclusiones: El empleo de Proctokinasa® resultó eficaz y seguro en el tratamiento de la enfermedad inflamatoria pélvica aguda grados I y II.

Introduction: Acute pelvic inflammatory disease is a common entity in young women of reproductive age and it is a leading cause of infertility. The search for an effective and safe anti-inflammatory treatment that relieves pain, avoids complications and sequels, it is priority for its treatment. Objective: To evaluate the efficacy and safety of the treatment with Proctokinasa® in acute pelvic inflammatory disease grades I and II. Materials and methods: An open, controlled clinical trial was carried out from January 2017 to January 2018 which included 76 patients diagnosed with acute pelvic inflammatory disease in primary health care; they were randomize assigned to two treatment groups: Proctokinasa® main group, who received one unity/8h for 2 days, and the Piroxican group, 1 suppository of 20 mg/24h per 7 days. The recommended oral antibiotic therapy was started simultaneously. Clinical and ultrasound response to treatment were evaluated. Adverse events were evaluated. Results: Clinical response was stated after 72 hours of treatment inmore than 50% of the patients in both groups, and it was 100% for the Proctokinasa® group in the last two evaluations (days 10 and 15). Remission of ultrasound alterations was evident in 96.9% of the Proctokinasa® group. Adverse events were few and mild. Conclusions: The use of Proctokinasa® was effective and safe in the treatment of acute pelvic inflammatory disease grades I and II.

The improving effect and mechanisms of Anshen Dingzhi Prescription on Alzheimer's disease-like behavior induced by D-galactose combined with AβO in mice / 药学学报

The purpose of this study was to explore the improving effect of Anshen Dingzhi Prescription (ADP) on Alzheimer's disease (AD)-like behavior in mice and its mechanisms. The main chemical components of ADP were identified by ultra performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The AD-like mouse model was induced by D-galactose (D-gal) combined with Aβ1-42 oligomer (AβO). The effect of ADP on AD-like behavior in mice was assessed using various behavioral experiments; pathomorphological changes in mouse hippocampal tissue were observed by Nissl staining and transmission electron microscopy; ELISA was used in the assessment of oxidative stress factors and inflammation-related factor levels; Western blot was performed to detect the expression of Aβ, Tau and glial fibrillary acidic protein (GFAP) proteins. The active components of ADP were screened according to TCMSP and HERB database, and the action targets of active components were predicted by Swiss Target Prediction platform. In addition, the targets of AD were predicted through DisGeNET database. Further, GO and KEGG enrichment analysis of common targets was carried out by Metascape database. Combined with the results of GO and KEGG analysis, in vivo experiments were carried out to explore the potential mechanism of ADP improving AD-like behavior in mice from the PI3K/Akt, calcium signal pathway and synaptic function. Finally, the core components of ADP were molecularly docked to the validated targets using Autodock Vina. Animal experiments were approved by the Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2021080). The results showed that the five chemical components, including ginsenoside Rg1, ginsenoside Rb1, tenuifolin, poricoic acid B and α-asarone were found in the ADP. ADP significantly improved the anxiety-like behavior and memory impairment, protected hippocampal neurons, decreased the levels of oxidative stress and inflammation, and inhibited the expression of Aβ and p-Tau induced by D-galactose combined with AβO in mice. The results of network pharmacology suggested that PI3K/Akt, calcium signal pathway and cell components related to postsynaptic membrane might be the key factors for ADP to improve AD. Animal experiments revealed that ADP up-regulated N-methyl-D-aspartate receptor 2A (GluN2A), postsynaptic density protein 95 (PSD95), calpain-1, phosphorylated protein kinase B (p-Akt), phosphorylated cAMP response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) expression and inhibited p-GluN2B and calpain-2 expression in the hippocampus of AD-like mice. The molecular docking results demonstrated that the core components of ADP, such as panaxacol, dehydroeburicoic acid, deoxyharringtonine, etc. had a high binding ability with the validated targets GRIN2A, GRIN2B, PSD95, etc. In summary, our results indicate ADP improves AD-like pathological and behavioral changes induced by D-galactose combined with AβO in mice, and the mechanism might be related to the NMDAR/calpain axis and Akt/CREB/BDNF pathway.

Experience of Medicinal Insects for Gynaecological Diseases / 中医杂志

It is believed that all kinds of gynaecological diseases are mostly related to deficiency and stagnation of qi and blood. Medicinal insects are good at running and scurrying， with the effectiveness of activating blood circulation and dispelling blood stasis， moving qi and relieving pain， searching and dredging collaterals， attacking hardness and dissipating mass， and purging foetus and resolving mass， etc. Appropriate prescriptions can enhance the effectiveness of the formula in eliminating blood stasis and eliminating stagnation. In the treatment of menstrual disorders， chronic pelvic inflammatory disease， uterine cavity disease， incomplete miscarriage， ectopic pregnancy， and other gynaecological diseases， medicinal insects including Quanxie （Scorpio）， Wugong （Scolopendra）， Tubiechong （Eupolyphaga/Steleophaga）， Jiuxiangchong （Coridius chinenses）， Shuizhi （Hirudo）， Mangchong （Tabanus）， Dilong （Pheretima） and other insects for medicinal purposes could be used， and the self-prescribed empirical formulas such as Sanhuang Decoction （三黄汤）， Hongteng Decoction （红藤汤）， Penning Decoction （盆宁方）， Shapei Decoction （杀胚方）， and Gongwaiyun Decoction （宫外孕方） and so on， were all applied medicinal insects and showed effective in clinic.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Chaihu Longgu Mulitang Relieves Generalized Anxiety Disorder in Rats via p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study whether Chaihu Longgu Mulitang can inhibit hypothalamic inflammation， mitigate anxiety-like behavior， and alleviate anxiety symptoms by regulating the p38 mitogen-activated protein kinase/nuclear factor-κB （p38 MAPK/NF-κB） signaling pathway in the rat model of generalized anxiety disorder （GAD）. MethodTwelve out of 74 Wistar rats were randomly selected as the blank group， and the remaining rats were subjected to chronic restraint stress for the modeling of GAD. The open field test （OFT） and elevated Porteus maze test （PMT） were conducted 14 days after modeling to detect the anxiety-like behaviors. Sixty successfully modeled rats were selected and randomized into model， low-， medium-， and high-dose （6， 12， and 24 g·kg-1， respectively） Chaihu Longgu Mulitang， and diazepam （1 mg·kg-1） groups （n=12） and administrated with corresponding drugs for 14 consecutive days. OFT and PMT were then carried out to examine the anxiety-like behaviors of the rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the hypothalamus and serum of rats were determined by the enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）was conducted to determine the mRNA levels of p38 MAPK， NF-κB p65， nuclear factor κB inhibitor α （IκBα）， and ionized calcium binding adaptor molecule 1 （Iba-1）. The protein levels of p38 MAPK， phosphorylated （p）-p38 MAPK， NF-κB p65， p-NF-κB p65， and IκBα in the hypothalamus of rats were determined by Western blot. The expression of Iba-1 in the hypothalamic microglia was detected by immunofluorescence assay. ResultCompared with the blank group， the model group had decreased body weight， scattered dark yellow fur， increased irritability， and preference to hibernation in the corner. In addition， the modeled rats showed increased edge movement distance and time in OFT （P<0.01） and decreased movement distance and time and the number of entries in the open arm in PMT （P<0.01）. The modeling increased the fluorescence intensity of Iba-1 in paraventricular nucleus of hypothalamus （P<0.01）， elevated the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamus （P<0.01）， up-regulated the protein and mRNA levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and down-regulated the protein and mRNA levels of IκBα （P<0.01） in the hypothalamus. Compared with the model group， medium- and high-dose Chaihu Longgu Mulitang and diazepam increased the body weight， improved the fur and behaviors， decreased the edge movement distance and time in OFT （P<0.05， P<0.01）， and increased the movement distance and time in the open arm in PMT （P<0.05， P<0.01）. Furthermore， they decreased the fluorescence intensity of Iba-1 in hypothalamic microglia （P<0.05， P<0.01）， lowered the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamic tissue （P<0.05， P<0.01）， down-regulated the mRNA and protein levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of IκBα （P<0.05， P<0.01） in the hypothalamus. ConclusionChaihu Longgu Mulitang can mitigate anxiety-like behaviors and relieve anxiety in GAD rats by inhibiting the p38 MAPK/NF-κB signaling pathway and reducing the activation of microglia and the levels of pro-inflammatory cytokines in the hypothalamus.

Research progress on association between macrophages and ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is an extremely complicated pathophysiological process, which may occur during the process of myocardial infarction, stroke, organ transplantation and temporary interruption of blood flow during surgery, etc. As key molecules of immune system, macrophages play a vital role in the pathogenesis of IRI. M1 macrophages are pro-inflammatory cells and participate in the elimination of pathogens. M2 macrophages exert anti-inflammatory effect and participate in tissue repair and remodeling and extracellular matrix remodeling. The balance between macrophage phenotypes is of significance for the outcome and treatment of IRI. This article reviewed the role of macrophages in IRI, including the balance between M1/M2 macrophage phenotype, the mechanism of infiltration and recruitment into different ischemic tissues. In addition, the potential therapeutic strategies of targeting macrophages during IRI were also discussed, aiming to provide reference for alleviating IRI and promoting tissue repair.

Effect of Zuogui Jiangtang Tongmai Prescription on Inflammatory Injury of Human Umbilical Vein Endothelial Cells Induced by High Glucose and LPS Based on GPR43/β-arrestin-2/IκBα/NF-κB Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects and mechanism of Zuogui Jiangtang Tongmai prescription （ZJTP） on human umbilical vein endothelial cells （HUVECs） damaged by high glucose combined with lipopolysaccharide （LPS）. MethodThe survival rate of cells was determined by cell counting kit-8 （CCK-8）， and the level of tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA） to determine the optimal injury concentration and action time of LPS， as well as the optimal action concentration of ZJTP drug-containing serum. HUVECs were divided into a blank control group， a model group， a ZJTP drug-containing serum group， and an SCFA mixed liquid group. ELISA was used to detect the level of endothelin-1 （ET-1）， nitric oxide （NO）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and TNF-α. Western blot was performed to detect the protein expression of G protein-coupled receptor43 （GPR43）， β-suppressor protein-2 （β-arrestin-2）， nuclear factor-κB suppressor α （IκBα）， and nuclear factor κB p65 （NF-κB p65）. The nucleation of NF-κB p65 was observed by immunofluorescence staining （IF）. The role of GPR43 in the regulation of inflammatory injury was observed by means of small interfering ribonucleic acid （siRNA）. The cells after intervention were divided into an empty carrier group， a ZJTP drug-containing serum group， a Si-GPR43 group， and a Si-GPR43 + ZJTP drug-containing serum group. The content of IL-1β， IL-6， and TNF-α was detected by ELISA. The protein expression of pathways was detected by Western blot. IF was used to observe the nucleation of NF-κB p65. ResultThe optimal molding condition was 1 mg·L-1 LPS for 24 h. The optimal drug intervention condition was 5% ZJTP drug-containing serum for 24 h. Compared with the blank control group， the content of ET-1 in the model group was significantly increased， and the content of NO was significantly decreased （P<0.01）. The levels of inflammatory factors were significantly increased （P<0.01）. The expressions of GPR43 and IκBα were significantly decreased， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly increased （P<0.01）. NF-κB p65 protein was transferred from the extranuclear to the intranuclear （P<0.01）. Compared with the model group， the content of ET-1 in the ZJTP drug-containing serum group was decreased， and the content of NO was increased （P<0.05）. The levels of inflammatory factors decreased （P<0.05）. The protein expressions of GPR43 and IκBα were increased， while the expressions of β-arrestin-2 and NF-κB p65 were decreased （P<0.05）. The amount of NF-κB p65 transferred from the intranuclear to the extranuclear decreased （P<0.01）. The mechanism study showed that compared with the Si-GPR43 group， the content of IL-1β， IL-6， and TNF-α were significantly decreased after treatment with ZJTP drug-containing serum （P<0.01）. The protein expressions of GPR43 and IκBα were significantly increased （P<0.01）， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly decreased （P<0.01）. The amount of NF-κB p65 transferred from the extranuclear to the intranuclear decreased （P<0.01）. ConclusionZJTP has a protective effect on HUVECs with high glucose and LPS-induced inflammatory injury， which may be related to the regulation of GPR43/β-arrestin-2/IκBα/NF-κB pathway.

Protective Mechanism of Paeoniflorin on Mice with Ulcerative Colitis Based on AMPK/mTOR Autophagy Pathway / 中国实验方剂学杂志

ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis （UC） through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS， and 56 BALB/c male mice were randomly divided into model group， AMPK inhibitor group （20 mg·kg-1）， paeoniflorin （50 mg·kg-1） + inhibitor （20 mg·kg-1） group， and high dose （50 mg·kg-1）， medium dose （25 mg·kg-1）， and low dose （12.5 mg·kg-1） paeoniflorin groups. After seven days of drug intervention， the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight， disease activity index （DAI） changes， and Hematoxylin-eosin （HE） staining results. Enzyme linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of mice in each group， and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 （LC3） content in the colon， AMPK， mTOR proteins， and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot， and the mRNA expression levels of AMPK， mTOR， Beclin1， LC3， and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group showed a decrease in body mass， an increase in DAI score， and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum （P<0.01）， while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue， and those of p-mTOR/mTOR were up-regulated （P<0.01）. The mRNA expression levels of AMPK and LC3 were down-regulated， while the mRNA expression levels of mTOR and p62 were up-regulated （P<0.01）. Compared with the model group and the paeoniflorin + inhibitor group， the mice treated with paeoniflorin showed an increase in body mass， a decrease in DAI score， a reduction in pathological damage to colon tissue， and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum （P<0.05）. The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated， while the protein levels of p-mTOR/mTOR were down-regulated （P<0.01）. The mRNA expression levels of AMPK， Beclin1， and LC3 were up-regulated， while the mRNA expression of mTOR and p62 were down-regulated （P<0.01）. The colon tissue of the inhibitor group was severely damaged， and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.

Research progress on invasive cervical resorption / 口腔疾病防治

@#Tooth absorption can be divided into physiological absorption and pathological absorption. Root absorption of mature deciduous teeth is physiological absorption. Pathological absorption includes internal absorption and external absorption. Internal absorption, also known as intramedullary absorption, includes inflammatory absorption and alternative absorption. External tooth absorption originates from the outer surface of the root or the neck of the tooth and can be divided into inflammatory absorption, alternative absorption, pressure resorption and invasive cervical resorption. Invasive cervical resorption (ICR) is pathological damage caused by many factors, which usually begins in the cemento-enamel junction and extends peripherally or horizontally in the dentin. It hardly invades the pulp. Orthodontic devices, trauma, bleaching, systemic diseases, and the use of certain medications can all lead to invasive cervical resorption. The clinical manifestations of ICR are usually asymptomatic or not obvious, and most of which are found in imaging examinations. Because caries and internal absorption are often misdiagnosed through plain apical radiography, cone beam computed tomography (CBCT) can help to better understand the situation of invasive cervical resorption. Because the pathogenesis and etiology of invasive cervical resorption are not fully understood, clinical negligence and inadequate treatment of invasive cervical resorption can even cause unnecessary tooth loss. This article reviews the latest research progress on the histopathologic features, pathogenic mechanism, susceptibility factors, diagnosis and treatment of ICR, with special emphasis on susceptibility factors and their mechanisms.

Treatment of Inflammatory Bowel Disease by Targeting M1/M2 Macrophage Polarization Balance with Traditional Chinese Medicine and Active Components： A Review / 中国实验方剂学杂志

Inflammatory bowel disease （IBD）， consisting of ulcerative colitis and Crohn's disease， is a chronic relapsing inflammatory gastrointestinal disease closely associated with immune dysfunction. The pathogenesis of IBD is closely related to genetic susceptibility， immune system dysfunction， environmental change， and intestinal microbial dysbiosis. Modern research has found that macrophage polarization plays an important role in the development of IBD and can affect the level of inflammatory response， intestinal mucosal repair， and intestinal microbial balance， making it a potential target for IBD treatment. Increasing evidence suggests that traditional Chinese medicine and its active components can regulate macrophage polarization through multiple pathways and balance the M1/M2 macrophage ratio， thus inhibiting inflammatory response， promoting intestinal mucosal repair， and slowing down the progression of IBD. This article summarized the biological processes and targets involved in macrophage polarization and discussed its impact on IBD. It also provided a brief overview of the latest research on how traditional Chinese medicine and its active components can improve IBD by regulating macrophage polarization， so as to provide new directions and strategies for the clinical application of traditional Chinese medicine in IBD treatment.